Genomic Predictors of Recurrent Pregnancy Loss (GPRPL)

• ClinicalTrials.gov Identifier: NCT05444283
• Recruitment Status: Active, not recruiting
• First Posted: July 5, 2022
• Last Update Posted: July 5, 2022
• Sponsor: Yale University
• Collaborators: Augusta University; Johns Hopkins University; University of Texas at Austin; Penn State University; University of Illinois at Chicago; Northwestern University; The University of Texas Health Science Center at San Antonio; Wayne State University; Columbia University; University of Colorado, Denver; University of Oklahoma
• Information provided by (Responsible Party): Yale University

Study Description

Brief Summary:

The overall goals of this proposal are to determine the genetic architecture of recurrent pregnancy loss (RPL) and to discover genomic predictors of RPL.

Condition or disease
Recurrent Pregnancy Loss

Detailed Description:

The following specific aims are proposed:

Aim 1: Collect clinically well-characterized samples from trios (product of conception (POC), biological mother, and biological father) with unexplained RPL. Specifically, a cohort of 1,000 trios that are rigorously-phenotyped will be recruited, and for which couples' RPL is not attributable to known causes. The POC and parental blood samples will be collected. Establishing cell lines from the POC if technically feasible will be considered. If it is necessary for the purpose of determining the pathogenicity of sequence variants from the trio, collecting blood samples from other family members after consent will also be considered. The study team may also request DNA or POC tissues from a prior pregnancy loss(es) if available.

Aim 2: A whole genome sequencing (WGS) at the Yale Center for Genome Analysis (YCGA) will be performed and bioinformatic analyses to identify pathogenic variants in included trios will performed as well. Pathogenic variants will be comprehensively defined and fully annotated variant maps in all included trios to provide the substrate for subsequent novel gene discovery, and ultimately, the development of clinical diagnostic tests will be generated.

Study Design

• Study Type: Observational
• Estimated Enrollment: 1000 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Large Scale Genome Sequencing and Integrative Analyses to Define Genomic Predictors of Recurrent Pregnancy Loss
• Actual Study Start Date: September 1, 2021
• Estimated Primary Completion Date: September 2026
• Estimated Study Completion Date: September 2026

Groups and Cohorts

Outcome Measures

Primary Outcome Measures :

1. Determine genetic etiology for Recurrent Pregnancy Loss [ Time Frame: 5 years ]
   The WGS tool will be used to analyze the POC sample and parental blood samples to determine the clinical reportable genetic cause for RPL

Biospecimen Retention:   Samples With DNA

Products of conception and blood of both biological parents

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 40 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes
• Sampling Method: Non-Probability Sample

Study Population

Couples who have had two or more previous pregnancy losses and have undiagnosed cause of recurrent pregnancy loss.

Criteria

Current qualifying pregnancy

• Loss of a current singleton pregnancy at < 20 0/7 weeks gestation (documented by ultrasonography or histopathological examination)
• Date of diagnosis
• Estimated gestational age by clinical EDD at time of diagnosis < 20 0/7 weeks
• Estimated gestational age by ultrasound at time of diagnosis
• Two or more prior pregnancy losses ("Previous Pregnancy History" eCRF to be completed about each prior pregnancy)
• No use of donor egg or donor sperm
• Chromosome microarray (chromosome karyotype to also be performed, if indicated on a case-by-case basis): Date, result; or unknown (not yet performed; to be performed at Yale)

RPL evaluation

• Parental karyotypes and/or microarray must not have revealed a pathogenic/likely pathogenic finding (such as an unbalanced translocation) for either biological parent:

  • Maternal: result and date
  • Paternal: result and date
• Lupus anticoagulant test: Value and date
• Anticardiolipin IgG < 40 GPL AND IgM < MPL; OR both < 99th percentile: Value and date
• Anti β2 glycoprotein IgM and IgG antibodies< 99th percentile: Value and date
• TSH: Value and date
• HgbA1C: Value and date
• Hysterosalpingogram or Sonohysterogram: Result (must not reveal evidence of uterine anomaly) and date
• No Type 1 or 2 diabetes considered poorly controlled (HgbA1C > 6.5)
• No history of autoimmune disease (e.g., SLE, RA, etc.)
• No history of cervical insufficiency

Contacts and Locations

Locations

United States, Connecticut

Yale University

New Haven, Connecticut, United States, 06511

Sponsors and Collaborators

Yale University

Augusta University

Johns Hopkins University

University of Texas at Austin

Penn State University

University of Illinois at Chicago

Northwestern University

The University of Texas Health Science Center at San Antonio

Wayne State University

Columbia University

University of Colorado, Denver

University of Oklahoma

More Information

• Responsible Party: Yale University
• ClinicalTrials.gov Identifier: NCT05444283
• Other Study ID Numbers: HIC# 2000029802
• First Posted: July 5, 2022
• Last Update Posted: July 5, 2022
• Last Verified: June 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Abortion, Spontaneous; Fetal Death; Abortion, Habitual; Recurrence; Disease Attributes; Pathologic Processes; Pregnancy Complications; Death